Objectives: To compare hypoglycemic warning symptoms (main objective) and incidence of severe hypoglycemia (secondary objective) between patients treated with animal and human insulin preparations. Research Design And Methods: Two hundred forty-seven patients on treatment with animal insulin preparations and 276 patients on human insulins, matched for duration of diabetes (16 ± 11 vs. 15 ± 10 yr), were recruited for the study. Patients were interviewed with a standardized questionnaire. Results: When asked which symptom usually occurs first during hypoglycemia, 19% of the animal insulin group and 22% of the human insulin group answered “sweating,” 19 and 17%, respectively, answered “trembling,” and 15 and 11%, respectively, answered “unrest.” According to the patients' perception, in both groups, their most reliable hypoglycemic warning symptoms were “trembling” (26 and 22%) and “sweating” (15 and 18%). Six and eight percent of patients, respectively, reported hypoglycemia unawareness and 17 and 18%, respectively, impaired awareness of hypoglycemia. The incidence of severe hypoglycemia was 0.45 cases/patient-yr in patients treated with animal insulins and 0.46 cases/patient-yr in patients treated with human insulin preparations. The differences were not statistically significant. Conclusions: This study shows that hypoglycemic warning symptoms and the incidence of severe hypoglycemia are comparable between patients on treatment with human and animal insulin preparations.